Viral contamination of cellular media and supernatants poses a challenge to biopharmaceutical manufacturers worldwide. Several methods have been employed to inactivate and/or remove large or small, enveloped or non-enveloped (or “naked”) DNA or RNA viral particles from cellular supernatants. Examples of these approaches include 20 nm filtration technology, anion-exchange membrane chromatography, low pH incubation and depth filter technology.
In addition to the above techniques, ultraviolet light has also been used to treat protein-containing solutions in order to inactivate viruses. In order to achieve efficient viral inactivation, however, the solution must be exposed to a sufficient dose of UV light, in the UV-C band. In some instances, the desired level of UV-C light exposure can cause undesirable modification and/or degradation of the protein in the solution. For example, in some cases reactive species may form in the solution and result in indirect oxidation or modification of proteins in the solution; other mechanisms for indirect modification due to UV-C exposure are also possible. See, e.g., Cabiscol, et al., (2010) Int. Microbiol, 3:315; Bandyopadhyay et al. (1999) Curr. Sci. 77:658-666; Schoneich, (2005) Biochim Biophys Acta 1703:111-19; Stadtman et al., (2003) Antioxid. Redox. Signal 5:577-82; Stadtman, (1993) Ann. Rev. Biochem. 62:797-821; and Dean et al., (1997) Biochem. J. 324:1-18.
The present disclosure addresses these and other challenges by providing methods of reducing oxidation, modification and degradation of protein in a solution exposed to UV band light, and more particularly UV-C light. Exposure to UV-C can be, as described, a component of a viral inactivation operation, and the protein in the solution can be of any type, for example a protein such as an antigen binding protein (e.g., one or more of (i) an antigen binding protein comprising one or more of a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a recombinant antibody, a single chain antibody, a diabody, a triabody, a tetrabody, a Fab fragment, a F(ab′)2 fragment, an IgD antibody, an IgE antibody, an IgM antibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody, and fragments thereof, (ii) an Fc domain; (iii) a peptide; (iv) an Fc fusion protein; and (v) a therapeutic protein).